Download ESIAD_Pipeline-Pancreatic_Ahlquist_FINAL v4

Pancreatic Cancer
Screening
v
Pancreatic cancer:
One of America’s most lethal cancers
48,960
new cases per year
40,560
deaths per year
Source: Am Cancer Soc. Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015.
Collaborating to detect pancreatic cancer early
•  Leveraging long-standing relationship and
building on success of Cologuard®
•  Significant intellectual property portfolio
•  Proprietary know-how and biospecimens
•  World leadership in cancer care through early detection
Pancreatic
Cancer Screening
David A. Ahlquist, MD
Gastroenterologist,
Gatton Professor of
Digestive Diseases Research,
v
Mayo Clinic
US mortality from pancreatic cancer rapidly increasing
•  Current: 4th leading cause
of cancer deaths
•  2020: Increases by 70%
(from 2010 levels) to
become 2nd leading
cause of cancer deaths
Projected cancer deaths (Thousands)
170
Lung & Bronchus
160
150
140
80
Pancreas
70
Colon & Rectum
60
50
Liver
Breast
40
Prostate
30
20
10
0
2010
2020
Breast
Liver and intrahepatic bile duct
Prostate
Source: *Rahib et al. Cancer Res 2014;74:2913
2030
Colon and rectum
Pancreas
Lung and bronchus
Two target lesions for early detection
•  Earliest stage pancreatic cancer
–  Pre-symptomatic, Stage I
–  Challenges
§  No effective population screening tool
§  May appear as small nodules or cysts
on imaging
§  Current tests inaccurate and
potentially dangerous
•  Pancreatic precancers
–  Cystic lesions
–  Challenges
§  Most incidentally found
§  Most do not progress
§  Unclear diagnosis and treatment
management
Urgency to detect pancreatic cancer in earliest stage
3 out of 4
<5 out of 100
survive 5 years if
asymptomatic with
survive 5 years if
diagnosed with
Stage I
Stages II, III or IV
Source: SEER 18 2004-2010
Challenges with current diagnostic approach
•  >600,000 incidental pancreatic
lesions in US per year
-  5-15% of all abdominal
CT or MRI scans
Fine Needle Aspirate (FNA)
•  Limited accuracy of endoscopy
and FNA
Mass/nodule
50-75%
Cyst
30%
Image courtesy of The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Translating diagnostic challenges into opportunities
Issues
Accuracy
Current Approach
Future Test
Fine Needle Aspirate
Pancreatic Juice
Suboptimal
(results in under/over Rx)
Potentially High
Morbidity
<5%
<1%
Endoscopic ultrasound
facility needed
Yes
No
Special training
Yes
No
Requires anesthesiologist
Yes
No
Collecting pancreatic juice during endoscopy
•  Pancreatic juice easily collected
as part of a routine endoscopy
–  Secretin I.V. stimulates immediate
pancreatic juice outflow
–  Juice collected from duodenum
through endoscope
•  Avoids
–  Risks with biopsy/FNA
–  Anesthetist coverage
–  Complex endoscopy
(endoscopic ultrasound)
Our approach to detection with pancreatic juice
• 
✓
• 
✓
Identified and secured best-in-class markers*
–  Whole methylome discovery
–  Comprehensive tissue validation
Cancer vs. Normal Tissue
Best candidate markers show
nearly perfect discrimination
Established feasibility*
–  Best individual meth DNA markers highly
discriminant in pancreatic juice (e.g., CD1D)
• 
✓
Optimized marker combinations and methods
–  Best 4-marker combination
• 
Sensitivity
96%
Specificity
97%
Validate performance in well-designed clinical
case-control study
Sources: *Kisiel et al. Clin Cancer Res 2015
PMID:26023084.DOI:10.1158/1078-0432.CCR-14-2469
Meth CD1D levels
in pancreatic juice
Molecular pancreatic juice testing
Indication: Diagnostic evaluation and monitoring of pancreatic lesions
•  Cysts
•  Small solid nodules
•  Large masses
Action:
+
Surgery, treatment, palliative care, observation
-
Monitor
Mayo Clinic 3-site prospective study underway
•  Primary aim
–  Assess accuracy of methylated DNA markers in pancreatic juice to detect
cancer and high-grade dysplasia
N=300
Pancreatic cancer cases (100)
Pancreatic cysts (100)
Normal controls (100)
•  Biospecimens collected: pancreatic juice, cyst fluid, stool and blood
Expanding opportunities for new molecular tools
•  Evaluation of nodules/cysts (near-term)
DNA Marker Copies in Stool
-  Pancreatic juice
•  Population cancer screening (longer-term)
-  Stool
§  Early studies suggest feasibility1
§  Optimal markers & methods needed
-  Blood
§  83% detection accuracy (combined stages)
in pilot study using plasma assay of meth
DNA markers, reported2
P<0.0001
50
40
30
20
10
§  Optimal markers and methods needed
0
PanC
Sources: *Kisiel et al. Cancer 2012;118:2623
** Kisiel et al. AACR 2015
Controls
Goals of molecular testing in pancreatic juice
Improved
Accuracy
Early
Detection
Reduced
Procedures
LDT
Opportunity
US market opportunity to detect pancreatic cancer
Diagnosing pancreatic
cysts for high-grade
# of Patients with Cysts
that need Monitoring
US Market Opportunity
550-650K
$500M+